The present invention relates to a method of treating noninflammatory acne.
Acne vulgaris is a common dermatological disorder which affects large patient populations in the preadolescent, adolescent and young adult age groups. Since it occurs primarily in the face and trunk areas of the body, the condition probably causes more mental pain and anguish than many other diseases which have an affect on an individual's physical appearance. Two types of skin lesions are observed in acne vulgaris: (1) non-inflammatory lesions which include open (blackhead) and closed (whitehead) comedones and (2) inflammatory lesions which include papules and pustules. The most severe form of acne is known as acne conglobata or nodulocystic acne. Acne conglobata patients, in addition to having comedones, papules and pustules, suffer from large inflammatory nodules and draining sinuses.
Acne develops in the sebaceous follicle and is initiated by an abnormal keratinization process in which epithelial cells, keratin and sebum adhere together and become impacted forming the initial lesion in acne, the microcomedo. When the normal flow of sebum to the skin surface is blocked by the microcomedo, the follicle begins to enlarge and forms non-inflammatory open (blackhead) and/or closed (whitehead) comedones. The inflammatory phase of acne is initiated when the follicular epithelium surrounding the non-inflammatory comedones ruptures to form inflamed papules, pustules and cysts.
Therapy for non-inflammatory acne lesions generally involves local administration of an agent which causes an exfoliation of the follicular keratinous impaction and thereby exerts a comedolytic effect on comedones. Alltrans-retinoic acid is a widely used topical comedolytic agent. Prolonged use of the compound, however, produces varying degrees of erythema and desquamation which are often accompanied by stinging and burning. Appropriate therapy for inflammatory lesions generally involves local and/or systemic administration of various agents. Topical pharmacologic agents which are used to treat inflamed pustules and papules include benzoyl peroxide and the tetracyclines. Oral erythromycin has also been shown to be useful in resolving inflammatory lesions.
The systemic administration of large doses of vitamin A (also known as retinol) have been reported to be useful in the treatment of acne (Straumford, J. V., "Vitamin A: Its Effect on Acne," Northwest Med., 42:219, 1943). More recently, Kligman et al. reported that large oral doses of vitamin A, 300,000 International Units and 500,000 International Units, were beneficial in the treatment of severe inflammatory acne (Kligman, A. M. et al., "Oral Vitamin A in Acne Vulgaris", Intl. J. Dermatol., 20:278, 1981.
The systemic administration of 13-cis-retinoic acid has been found to be effective when administered orally to patients with severe inflammatory cystic acne (Peck, G. L. et al., "Prolonged Remissions of Cystic Acne and Conglobate Acne with 13-Cis-Retinoic Acid", New Eng. J. Med., 300:329, 1979). In addition, oral administration of 13-cis-retinoic acid has been reported to be effective in the management of certain disorders of keratinization including basal cell carcinoma and keratoacanthoma (Haydey, R. P. et al., Treatment of Keratocanthomas With Oral 13-Cis-Retinoic Acid", New Eng. J. Med; 303, 1980). Topical administration of vitamin A acid has been reported by A. M. Kligman et al. to be effective in the treatment of open and closed comedones associated with acne ("Topical Vitamin A Acid in Acne Vulgaris", Arch. Derm. 99:469, 1969). The effectiveness of this treatment as disclosed by A. M. Kligman in U. S. Pat. No. 3,729,569 (Apr. 24, 1973) is apparently accompanied by the irritation effects associated with vitamin A acid.
Thus acne can be subdivided into two categories, inflammatory acne and non-inflammatory acne, based on both pathophysiological and therapeutic differences. Drugs that are effective, both orally and topically, in the treatment of inflammatory acne (e.g., benzoyl peroxide and the antibiotics) are clearly not effective in the treatment of comedogenic or non-inflammatory acne. On the other hand, drugs which have comedolytic activity (e.g., salicylic acid and all-trans vitamin A acid) and which are effective in treating non-inflammatory acne, are not effective in treating inflammatory acne.